Stabilization and controlled-release of basic fibroblast growth factor by water-insoluble aluminum salts of cyclodextrin sulfates.

Cyclodextrin Drug Carrier Systems

“…Oral administration of sucralfate elevates local levels of basic fibroblast growth factor in the ulcer bed, indicating that sucralfate acts as a potent angiogenesis stimulator, primarily on the basis of its ability to stabilize and slowly release locally available basic fibroblast growth factor. As described previously, the aluminum salt of β-cyclodextrin sulfate is a more potent stabilizer and sustained-release carrier for basic fibroblast growth factor than sucralfate . The rigid macrocyclic structure of β-cyclodextrin sulfate imposes spatial constraints on the sulfate groups, which enhances the charge density and the affinity for basic fibroblast growth factor.…”

“…A water-insoluble aluminum salt of β-cyclodextrin sulfate was prepared, and its possible utility as a stabilizer and sustained-release carrier for basic fibroblast growth factor was evaluated. , An adsorbate of basic fibroblast growth factor with the aluminum salt of β-cyclodextrin sulfate was prepared by incubating the protein with a suspension of the aluminum salt of β-cyclodextrin sulfate in water. The mitogenic activity of basic fibroblast growth factor released from the adsorbate, as indicated by the proliferation of kidney cells of baby hamsters (BHK-21), was almost comparable with that of the intact protein.…”

“…The oral administration of the aluminum salt of β-cyclodextrin sulfate tended to enhance the healing rate of acetic acid-induced gastric ulcers and cysteamine-induced duodenal ulcers, probably in a similar manner as sucralfate does. In particular, the oral administration of the aluminum salt of β-cyclodextrin sulfate loaded with basic fibroblast growth factor had the most prominent healing effects on the ulcers …”

Pharmaceutical Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation

“…Recent studies have also shown that an insoluble, sulfated polymer of -CD, when applied periadventitially to rats that have undergone carotid artery balloon injury, inhibited intimal thickening in a sustained fashion, suggesting that cellular processes mediated by heparin binding growth factors may be modulated by S--CD. 192 Our previous studies have shown that S-CDs, when given intraperitoneally, protected rats against renal impairment due to gentamicin, an antibiotic aminoglycoside, but the other hydrophilic CDs were ineffective. 111 A hypothesis is proposed to provide a common mechanism for conventional anti-ulcer therapy in which endogenous growth factors, such as basic fibroblast growth factor (bFGF), play a central role.…”

“…Recent studies have demonstrated that S--CD, a synthetic heparin substitute, inhibited smooth muscle cell migration and proliferation in vitro and its oral administration reduced both intimal hyperplasia and angiographic evidence of restenosis in an experimental angioplasty restenosis model in rabbits. 191,192 The rigid macrocyclic structure of S--CD imposes spatial constraints on the sulfate groups, which enhances the charge density and the affinity for bFGF. Recent studies have also shown that an insoluble, sulfated polymer of -CD, when applied periadventitially to rats that have undergone carotid artery balloon injury, inhibited intimal thickening in a sustained fashion, suggesting that cellular processes mediated by heparin binding growth factors may be modulated by S--CD.…”